The Targeting Activity of Co-chaperones

The question of how DnaJ proteins interact with substrates and mediate their transfer onto Hsp70 partner proteins is not answered for any of the three classes of DnaJ proteins. Some DnaJ homologs have broad substrate specificity, such as E. coli DnaJ and yeast Ydjl, while others have more restricted substrate spectra. In particular the DnaJ proteins of class III may either bind a restricted number of substrates, such as the clathrin-specific auxilin or the kinesin light chain, or they may not bind substrates themselves but rather are positioned in close proximity to substrates. The latter seems to be the case for Dj 1A in the plasma membrane of E. coli (Clarke et al, 1997 Kelley and Georgopoulos, 1997a), Sec63 at the translocation pore in the ER (Corsi and Schekman, 1996 Rapoport et al., 1996), and cysteine string proteins on the surface of neurosecretory vesicles (Buchner and Bundersen, 1997). 

Structural information is available for the J domains of E. coli DnaJ, human DjBl/Hdj-1, and polyomavirus T-antigen (Szyperski et al., 1994 Pellecchia et al., 1996 Qian et al., 1996 Beijanskii et al., 2000 see Section III.B.2.b), the Zn-binding domain of E. coli DnaJ (residues 121— 209 Martinez-Yamout et al., 2000), and the C-terminal domain of yeast Sisl (residues 171-352) which has homology to the C-terminal domain 

Bag proteins differ from GrpE proteins by virtue of their ability to associate with ligands other than Hsp70 proteins. Although not shown experimentally, it is generally assumed that Bag proteins use this ability 

The family of Bag proteins is composed of the homologs Bag-1, Bag-2, Bag-3 (CAIR/BIS), Bag-4 (SODD), Bag-5, and Bag-6 (BAT3/Scythe) 

The 35-kDa protein Chip is the most recently discovered co-chaperone of eukaryotic Hsp70s (Fig. 5). Chip inhibits the in vitro chaperone activity of Hsc70 and Hsp70 in preventing the aggregation of denatured 

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